Intense Radiotherapy Slows Prostate Cancer Growth

Intense, highly focused doses of radiotherapy may slow disease progression in men with hormone-sensitive metastatic prostate cancer, according to findings from a phase II clinical trial. The results suggest that stereotactic ablative radiotherapy (SABR), versus observation, may allow some patients to delay androgen deprivation therapy (ADT), which is associated with significant adverse effects and health risks.

The ORIOLE trial compared SABR—which typically requires 5 or fewer treatments compared with an average of 20 to 30 for standard radiotherapy—with observation in 54 men with hormone-sensitive oligometastatic prostate cancer with three or fewer metastases. All patients previously had surgery or radiotherapy to treat their primary tumors but had not received ADT or other systemic therapy to treat metastases within 6 months of enrollment.

After 6 months, seven of 36 patients (19%) receiving SABR experienced disease progression compared with 11 of 18 patients (61%) in the observation arm. In addition, SABR induced a systemic immune response, and researchers identified a set of high-risk mutations that might predict which patients are most likely to benefit from the therapy.

Although the approach is controversial, many men are interested in delaying ADT as long as possible, the authors note. The treatment is associated with a range of side effects including erectile dysfunction, bone fractures, insulin resistance, gynecomastia, and loss of muscle mass, among others.

“Our findings show that SABR prevents disease progression in men with oligometastatic prostate cancer and can allow some men to forestall initiation of lifelong ADT,” says senior investigator Phuoc T. Tran, MD, PhD, of Johns Hopkins Medicine in Baltimore, MD. “This trial adds to growing data supporting clinical-practice change; however, we are awaiting validation in larger phase III trials.”

Prostate-specific membrane antigen (PSMA)-targeted PET scans performed in the SABR arm after randomization and at 180 days revealed that 16 men (44%) had baseline lesions, data that were not available to investigators during treatment planning, according to the study. Men with at least one untreated lesion at baseline were significantly more likely to have disease progression at 6 months, suggesting that advanced imaging could potentially improve outcomes through earlier detection and treatment of small lesions.

“These findings might have been even more dramatic if new and more-sensitive imaging technologies, such as PSMA-targeted PET, were used from the beginning to include or exclude patients from the trial,” notes Andrew C. Hsieh, MD, of Fred Hutchinson Cancer Research Center in Seattle, WA. “This is important because the lower limit of detection of standard imaging techniques may lead to undetected, and therefore untreated, oligometastatic disease.”

After treatment, investigators analyzed patients' white blood cells and found an expanded population of T cells, suggesting that SABR can trigger a full-body immune response, notes Tran. This observation underscores the value of ongoing studies examining the combination of radiation, including SABR, with immunotherapies, ranging from immune checkpoint blockers to cellular therapies.

The ORIOLE trial indicates that some patients can delay ADT, says Hsieh. However, given the relatively short follow-up period and the crossover from the observation arm—nearly all patients in this group eventually received SABR—it remains unclear whether patients with oligometastatic disease can be cured with SABR.

“Future studies with or without SABR in combination with immune therapies are needed to determine if irradiating metastatic lesions can improve the therapeutic response,” says Hsieh. –Janet Colwell